1. Field of the Invention
This invention relates to implantable devices capable of delivering liquid substances, such as drugs, to the peritoneal cavity or other sites in the body where the device has been implanted. More particularly, this invention relates to implantable devices which are capable of promoting ingrowth of connective tissue and which thereby become incorporated into the tissues of the body.
2. Statement of the Art
The necessity to achieve adequate, safe, and convenient administration of drug therapy to patients, particularly diabetic patients, has lead to the development of devices which deliver a predetermined dosage or amount of drug to the patient over a required amount of time. Initially, these devices were typically extracorporeal units comprising a source or reservoir of drug, a catheter, and a pump for controlled delivery. Recently, research and development in drug delivery devices has been focused on implantable devices which will lead to more convenient drug therapy for patients.
Insulin-dependent diabetic patients, for example, typically have been required to undergo daily injections of insulin. Daily injections often prove to be difficult or unsatisfactory for a number of reasons. For many patients, self-administration of an injection is difficult and they must depend upon another person to give them the injection. The frequency with which subcutaneous injections must be given leads to soreness of the usual injection site. Often, injections of the drug are made peritoneally while the site normally used for injection heals. More importantly, studies have indicated that a single injection in a twenty-four hour period does not provide an optimal or equilibrated dose of insulin to a patient because very high blood levels are initially experienced, leaving inadequate amounts of insulin in the body for later meals, such as lunch and dinner.
For these and other reasons, attempts have been made to develop a device which could produce a controlled and somewhat constant flow of insulin to the patient. Extracorporeal devices were initially developed in which medication was delivered via a catheter permanently or semi-permanently implanted in a vein, in a muscle, or in the peritoneum of the patient (e.g., U.S. Pat. No. 4,723,947 to Konopka). The patient or caregiver typically would preprandially determine an amount of insulin needed, based on the projected amount of caloric intake for the particular meal, and the required amount of drug would be delivered to the patient by injection or pumping means. These devices required the patient to carry the necessary equipment of the device on or near his or her person, such as on a specialized belt.
Other extracorporeal devices were developed, such as the transdermal patch filled with drug, which, when affixed to the wearer's skin, would slowly diffuse drug through the skin and into the body (e.g., U.S. Pat. No. 4,687,481 to Nuwayser). Despite the success achieved in delivering a more suitable dosage of drug pursuant to the patient's immediate needs, the obvious inconvenience of extracorporeal drug delivery devices lead to the development of implantable devices.
Delivering a medication, such as insulin, into the body via an implantable device has been approached in several different ways. For example, devices have been developed where the patient ingests a predetermined dose of medication enveloped in a special covering which expands upon contact with body fluids thereby keeping the device within the body long enough to effect a long-term administration of the medication. (U.S. Pat. No. 4,207,390 to Mamajek)
More frequently, implantable devices have been developed which must be surgically inserted into a body cavity of the patient. Examples of such devices are disclosed in U.S. Pat. No. 4,069,307 to Higuchi, et al. (ethylene-vinyl acetate copolymer reservoir of drug which operates by diffusion); U.S. Pat. No. 4,180,560 to Katz et al. (spherical implantable pellets); U.S. Pat. No. 4,557,724 to Gregonis, et al. (refillable implantable reservoir of drug placed in contact with peritoneal cavity); U.S. Pat. No. 4,624,847 to Ayer et al. (osmotic dispensing device implantable in the peritoneal cavity); U.S. Pat. No. 4,684,524 to Eckenhoff et al. (implantable dispenser of heat-responsive composition diffused by osmotic processes); U.S. Pat. No. 4,826,480 to Diaz et al. (implantable catheter).
A common problem encountered with implantable devices has been overgrowth of the device by dense fibrotic tissue having little or no vascularization--a process called "encapsulation." More specifically, encapsulation occurs when a foreign object is placed in the body. Connective tissue begins to grow about the foreign object, and as the connective tissue matures, it loses its vascularization and becomes thick scar tissue. Encapsulation of implantable devices results in either occlusion of the drug outlet system or overgrowth of the entire device so that no drug can escape the encapsulated area. Encapsulation is particularly troublesome where only a small flow of drug is being delivered through the device.
Because encapsulation typically occurs where there is a continuous surface upon which the tissue can migrate, different approaches have been taken to limit or inhibit encapsulation of implanted devices. For example, the shape of some implantable devices has been modified to reduce sharp edges which, it appears, tend to enhance encapsulation. Materials which discourage encapsulation have been used preferentially. Even with attention to design parameters, however, encapsulation of implantable devices has proved to be the limiting factor in efficacy of implantable devices.